Immunogenic composition

Abstract

The present application relates to an immunogenic composition comprising at least 2 conjugates of N. meningitidis capsular saccharide and protein carrier, wherein said conjugates comprise at least 2 different N. meningitidis capsular saccharides selected from the group consisting of MenA, MenC, MenY and MenW, wherein at least one capsular saccharide is conjugated to a protein carrier with a saccharide:protein ratio (w/w) between 1:2-1:5, and wherein at least one different capsular saccharide is conjugated to a protein carrier with a saccharide:protein ratio (w/w) between 5:1-1:1.99.

The invention claimed is: 
     
       1. An immunogenic composition comprising conjugates of a plurality of  N. meningitidis  capsular saccharides and carrier protein, wherein said conjugates comprise a first  N. meningitidis  capsular saccharide which is  N. meningitidis  serogroup A capsular saccharide (MenA) or  N. meningitidis  serogroup C capsular saccharide (MenC), wherein the first  N. meningitidis  capsular saccharide is conjugated to a first carrier protein with a saccharide to carrier protein ratio (w/w) ranging from 1:2-1:5, and a second different  N. meningitidis  capsular saccharide conjugated to a second carrier protein with a saccharide to carrier protein ratio (w/w) ranging from 5:1-1:1.99, wherein the second different capsular saccharide is a  N. meningitidis  serogroup Y capsular saccharide (MenY), a  N. meningitidis  serogroup W capsular saccharide (MenW) or a  N. meningitidis  serogroup C capsular saccharide (MenC), wherein the first  N. meningitidis  capsular saccharide is conjugated to a linker with 1-cyano-4-dimethylamino pyridinium tetrafluoroborate (CDAP) chemistry, wherein the first carrier protein is conjugated to the linker with carbodiimide chemistry, optionally using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC), and wherein the composition does not include an adjuvant. 
     
     
       2. The immunogenic composition of  claim 1 , wherein the first  N. meningitidis  capsular saccharide is  N. meningitidis  serogroup A capsular saccharide (MenA) and the second different  N. meningitidis  capsular saccharide is  N. meningitidis  serogroup W capsular saccharide (MenW) and the ratio of the MenW capsular saccharide to the carrier protein ranges from 5:1-1:1.99, 2:1-1:1.99, 1.5:1-1:1.8, 1:1-1:1.7, 1:1.2-1:1.6, or 1:1.4-1:1.5 (w/w). 
     
     
       3. The immunogenic composition of  claim 1 , wherein the second  N. meningitidis  capsular saccharide is  N. meningitidis  serogroup Y capsular saccharide (MenY) and the ratio of the MenY capsular saccharide to the carrier protein ranges from 5:1-1:1.99, 2:1-1:1.99, 1.5:1-1:1.9, 1:1-1:1.8, 1:1.1-1:1.6, or 1:1.3-1:1.4 (w/w). 
     
     
       4. The immunogenic composition of  claim 2 , wherein the ratio of the  N. meningitidis  serogroup A capsular saccharide (MenA) to the carrier protein ranges from 1:2-1:5, 1:2.4-1:4, 1:2.7-1:3.5, or 1:2.9-1:3.1 (w/w). 
     
     
       5. The immunogenic composition of  claim 1 , wherein the first  N. meningitidis  capsular saccharide is  N. meningitidis  serogroup A capsular saccharide (MenA) and the second different  N. meningitidis  capsular saccharide is  N. meningitidis  serogroup C capsular saccharide (MenC) and the ratio of the MenC capsular saccharide to carrier protein ranges from 5:1-1:1.99, 2:1-1:1.99, 1.5;1-1:1.8, 1.3:1-1:1.6, 1.2:1-1:1.4, or 1.1:1-1:1.2 (w/w). 
     
     
       6. The immunogenic composition of  claim 1 , wherein the first  N. meningitidis  capsular saccharide is  N. meningitidis  serogroup C capsular saccharide (MenC) and the ratio of the MenC capsular saccharide to carrier protein ranges from 1:2-1:5, 1:2.5-1:4.5, 1:2.7-1:4.3, 1:3-1:4, or 1:3.3-1:3.5 (w/w). 
     
     
       7. The immunogenic composition of  claim 1 , wherein the second different  N. meningitidis  capsular saccharide is directly conjugated to the second carrier protein. 
     
     
       8. The immunogenic composition of  claim 1  wherein the first and second carrier proteins are independently selected from the group consisting of tetanus toxoid (TT), diphtheria toxoid (DT), cross-reacting material 197 (CRM197), fragment C of tetanus toxoid (TT) and protein D. 
     
     
       9. The immunogenic composition of  claim 8  wherein the first  N. meningitidis  capsular saccharide is conjugated to the first carrier protein and the second different  N. meningitidis  capsular saccharide is conjugated to the second carrier protein, wherein the first and second carrier proteins are the same carrier protein. 
     
     
       10. The immunogenic composition of  claim 1 , wherein the first  N. meningitidis  capsular saccharide is separately conjugated to the first carrier protein and the second different  N. meningitidis  capsular saccharide is separately conjugated to the second carrier protein. 
     
     
       11. The immunogenic composition of  claim 1 , further comprising a  H. influenzae  b capsular saccharide (Hib) conjugated to a carrier protein. 
     
     
       12. The immunogenic composition of  claim 11  wherein the  H. influenzae  b capsular saccharide (Hib) conjugate is present in a lower dose than the dose of each of the first capsular saccharide and the second different capsular saccharide conjugates. 
     
     
       13. The immunogenic composition of  claim 1  comprising a  N. meningitidis  serogroup B outer membrane vesicle preparation or capsular saccharide. 
     
     
       14. A vaccine comprising the immunogenic composition of  claim 1  and a pharmaceutically acceptable excipient. 
     
     
       15. A vaccine kit for concomitant or sequential administration comprising two multi-valent immunogenic compositions for conferring protection in a host against disease caused by  Bordetella pertussis, Clostridium tetani, Corynebacterium diphtheriae, Haemophilus influenzae  and  Neisseria meningitidis , said kit comprising a first container comprising tetanus toxoid (TT), diphtheria toxoid (DT), and whole-cell or acellular pertussis components and a second container comprising the immunogenic composition of  claim 1 . 
     
     
       16. A process for making the vaccine of  claim 14  comprising the step of mixing the immunogenic composition of  claim 1  with a pharmaceutically acceptable excipient. 
     
     
       17. A method of immunizing a human host against disease caused by  Neisseria meningitidis  infection comprising administering to the host an immunoprotective dose of the immunogenic composition of  claim 1 .